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S. Katta, I. Kaur, R. Reddy, R. Narayanan, A. Mathai, A. B. Majji, S. Chakrabarti; The del443ins54 Polymorphism in ARMS2 is Strongly Associated With Age-Related Macular Degeneration in an Indian Cohort. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1260.
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The ARMS2 gene on 10q26 has been implicated as the second major susceptibility gene for Age-Related Macular Degeneration (AMD). Globally, a coding (A69S) single nucleotide polymorphism (SNP) in ARMS2 (rs10490924) has been associated with increased risk of AMD. Following A69S, an insertion-deletion (indel) polymorphism that affects the stability of the mRNA by the removal of polyadenylation signal (443bps) and insertion of a 54bp AU rich element in the 3’UTR, was identified. The presence of this del443ins54 in homozygous condition increased the risk of AMD by several folds. Earlier we had demonstrated a significantly strong association of the A69S variant with AMD in an Indian cohort. We now aimed to determine the involvement of this indel variant with disease susceptibility in our cohort.
The del443ins54 was screened in a cohort of previously diagnosed AMD cases (n=250) and normal controls (n=250). Screening was accomplished by a combination of PCR-based agarose gel electrophoresis followed by validation of a subset of samples by resequencing. Genotypes were directly scored from the gel pattern. Allele, genotype frequencies, odds ratios and relative risks (RR) were calculated to assess the risk conferred by this indel variant.
The frequency of the insertion allele del443ins54 was significantly higher (p=1.27x10-18) among cases than controls (69.5% vs. 38.2%). Homozygosity of the insertion allele was strongly associated with an increased risk of AMD [OR=7.97, 95% CI, 4.55-13.95] compared to one copy of the insertion allele [OR=2.68, 95% CI, 1.57-4.57]. Similarly, the homozygous insertion allele exhibited a RR of 2.58 (95%CI, 1.91-3.49) that conferred a population attributable risk of 68%. Compared to our previously published data on ARMS2/HTRA1 SNPs, the del443ins54 exhibited an enhanced risk of AMD similar to the A69S (ARMS2) variant.
The present data provides an independent validation of the association of del443ins54 variant with AMD in an Indian cohort.
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